DNA damage deficiency in prostate cancer: functional characterisation and treatment

Sequencing profiling studies of prostate tumours have identified common alterations in genes involved in DNA damage response. Up to 10% of patients with aggressive disease show ATM loss. Clinically, tumours with defects in DNA repair
genes such as BRCA1/2 show exceptional responses to PARP inhibitors, while ATM mutant tumour response is variable. In this project we will use available complementary models from mouse and human prostate to investigate the
effect of ATM mutants and their interaction with other prostate cancer drivers on tumour progression and response totreatment with an aim to identify more effective therapies for patients.